Disease relevance of Itga7

• Absence of either dystrophin or alpha7 integrin results in a muscular dystrophy [1].
• Absence of alpha7 integrin in dystrophin-deficient mice causes a myopathy similar to Duchenne muscular dystrophy [1].
• Here, we show that, in clonally derived mouse K1735 melanoma variant cell lines with high (M-2) and low (C-23) metastatic potential, elevated expression of alpha7 correlates with reduced cell motility, metastasis, and tumor growth [2].
• Forced expression of alpha7 in the M-2 cells suppressed cell motility, tumor growth, and metastasis [2].
• Several alpha7 null embryos were identified with cerebrovascular hemorrhages and showed reduced vascular smooth muscle cells and cerebral vascularization [3].

Psychiatry related information on Itga7

• The presence of alpha 7* nicotinic receptors on cholinergic neurones may also render these cells specifically vulnerable to degeneration in Alzheimer's disease [4].
• The compounds were evaluated for binding to the alpha4beta2 and alpha7 nicotinic acetylcholine receptors (nAChRs), for pharmacological activity in the mouse tail-flick and hot-plate assays, and for hypothermia and locomotor activity [5].
• MATERIALS AND METHODS: Mice with targeted deletion of the gene coding for the alpha7 subunit of nicotinic receptors and wild-type controls were trained on a five-choice serial reaction time task with food reinforcers presented under varying parametric conditions [6].
• In the present study, we tested whether (-)-nicotine and U-50,488H prevent delayed-memory impairment induced by beta-amyloid peptide (25-35), and changes of expression of alpha7-type nicotinic acetylcholine receptor mRNA and prodynorphin mRNA [7].

High impact information on Itga7

• Surprisingly, mice homozygous for the mutation are viable and fertile, indicating that the alpha 7 beta 1 integrin is not essential for myogenesis [8].
• Absence of integrin alpha 7 causes a novel form of muscular dystrophy [8].
• Integrin alpha 7 beta 1 is a specific cellular receptor for the basement membrane protein laminin-1 (refs 1,2), as well as for the laminin isoforms -2 and -4 (ref. 3). The alpha 7 subunit is expressed mainly in skeletal and cardiac muscle and has been suggested to be involved in differentiation and migration processes during myogenesis [8].
• These findings demonstrate that alpha 7 beta 1 integrin represents an indispensable linkage between the muscle fibre and the extracellular matrix that is independent of the dystrophin-dystroglycan complex-mediated interaction of the cytoskeleton with the muscle basement membrane [8].
• Administration of nicotine, an alpha7 agonist that mimics vagus nerve stimulation, increases proinflammatory cytokine production and lethality from polymicrobial sepsis in splenectomized mice, indicating that the spleen is critical to the protective response of the cholinergic pathway [9].

Chemical compound and disease context of Itga7

• Alpha4 but not alpha3 and alpha7 nicotinic acetylcholine receptor subunits are lost from the temporal cortex in Alzheimer's disease [10].
• In vivo, methyllycaconitine (MLA), a specific alpha-7 nAChR antagonist, significantly prevented MDMA-induced neurotoxicity at dopaminergic but not at serotonergic level, without affecting MDMA-induced hyperthermia [11].
• In behavioral experiments, intrathecal (i.t.) injection of non-selective nAChR antagonist mecamylamine and alpha4beta2 subtype-selective antagonist dihydro-beta-erythroidine (DHbetaE) dose-dependently induced thermal and mechanical hyperalgesia in mice while the alpha7-selective antagonist methyllycaconitine (MLA) had no effect [12].

Biological context of Itga7

• The binding of Epibatidine and alphaBungarotoxin, ligands for alpha3- and alpha7-containing receptors, respectively, revealed, for each ligand, a single class of high-affinity binding sites, with similar affinity in both wild-type and mdx mice [13].
• Expression of the laminin-binding alpha7 integrin is tightly regulated during myogenic differentiation, reflecting required functions that range from cell motility to formation of stable myotendinous junctions [14].
• Functional analysis with site-specific deletions identified a specific double E-box sequence in the upstream promoter region (-2.0 to -2.6 kb) that is responsible for c-Myc-induced suppression of alpha7 expression [14].
• This report provides evidence that alpha7 gene expression during muscle differentiation is regulated by the c-Myc transcription factor [14].
• To ascertain whether integrin alpha7 upregulation compensates for the loss of the transmembrane sarcoglycan linkage in sarcoglycan-deficient muscle, we generated mice lacking both integrin alpha7 and gamma-sarcoglycan (gxi) [15].

Anatomical context of Itga7

• Muscle fibers from mdx/alpha7(-/-) mice exhibited extensive loss of membrane integrity, increased centrally located nuclei and inflammatory cell infiltrate, greater necrosis and increased muscle degeneration compared to mdx or alpha7-integrin null animals [16].
• Analysis of RNA from the hindlimbs of dy/dy mice demonstrated that in the absence of laminin alpha7 gene transcription is inhibited and limited to specific alternatively spliced isoforms [17].
• Dystrophin stabilizes alpha 3- but not alpha 7-containing nicotinic acetylcholine receptor subtypes at the postsynaptic apparatus in the mouse superior cervical ganglion [13].
• Muscle fibers attach to laminin in the basal lamina using two distinct mechanisms: the dystrophin glycoprotein complex and the alpha 7 beta 1 integrin [18].
• A new isoform of the laminin receptor integrin alpha 7 beta 1 is developmentally regulated in skeletal muscle [19].

Associations of Itga7 with chemical compounds

• Together, these findings indicate an essential role for integrin alpha7 in the maintenance of dystrophin-deficient muscles [1].
• RNA interference experiments show that the above nicotine-mediated process requires alpha7 nAChR [20].
• 32P label was rapidly removed from [32P]ADP-ribosylated integrin alpha 7 at either site of modification, a process inhibited by free ADP-ribose or p-nitrophenylthymidine-5'-monophosphate, an alternative substrate of 5'-nucleotide phosphodiesterase [21].
• Since ADP-ribosylarginine hydrolase, the enzyme responsible for cleavage of the ADP-ribosylarginine bond and a component with the transferase of a putative ADP-ribosylation cycle, is cytosolic, the processing of ADP-ribosylated integrin alpha 7 was investigated [21].
• Integrin alpha 7 is a major substrate in skeletal muscle cells for the cell surface, glycosylphosphatidylinositol-anchored, arginine-specific ADP-ribosyltransferase [21].

Regulatory relationships of Itga7

• Analysis of RNA from mdx mice and from patients with Duchenne and Becker muscular dystrophies indicates that the increase in the alpha7beta1 integrin is regulated at the level of alpha7 gene transcription [17].
• TGF-beta 1 regulates adhesion of mucosal mast cell homologues to laminin-1 through expression of integrin alpha 7 [22].
• By contrast, C-23 cells expressed low or undetectable levels of alpha1, alpha2, and alpha6 but had up-regulated levels of alpha7 [2].

Other interactions of Itga7

• Surprisingly, DKO mice survived post-natally and were indistinguishable from wild-type, integrin alpha7-deficient and mdx mice at birth, but died within 24-28 days [1].
• The alpha 7 beta 1 laminin receptor was proposed to be involved in myogenic differentiation [19].
• The N-terminal region of deltaEF1 is necessary for alpha7 repression, and this region also binds the co-activator p300/CBP [23].
• Vinculin is present throughout development of the myotendinous junction, suggesting that the alpha 7 integrin recognizes a preformed cytoskeletal structure [24].
• Conditioned dorsal root ganglia from normal mice cultured with a blocking antibody to beta1 integrin and from alpha7 integrin KO mice showed reduced axonal growth in both Matrigel- and laminin-supplemented collagen gels [25].

Analytical, diagnostic and therapeutic context of Itga7

• Reverse transcriptase-polymerase chain reaction analysis of alpha 7 mRNA indicated that the X1 and X2 isoforms were present in equal amounts in mouse skeletal myoblasts and adult heart [26].
• Mouse C2C12 and MM14 myoblast cell lines were found by flow cytometry and immunoprecipitation to express high levels of the alpha 7 integrin [27].
• Antibodies specific for alpha 7B integrin and in situ hybridization revealed the presence of alpha 7 mRNA and alpha 7B protein in the E10 myotome and later in primary and secondary myotubes [28].
• Chronic loading: (1) increased expression of alpha1, alpha5, and beta1 integrin transcripts and (2) increased protein expression of integrin subunits which are dominantly expressed in striated muscle (alpha7 and beta1D) both by western blotting and immunofluorescent microscopy [29].
• Axotomy led to a strong increase of this integrin on regenerating motor and sensory neurons, but not on the normally nonregenerating CNS neurons. alpha7 and beta1 subunits were present on the axons and their growth cones in the regenerating facial nerve [30].

References